Corticosteroid plus glycyrrhizin therapy for chronic drug‐ or herb‐induced liver injury achieves biochemical and histological improvements: a randomised open‐label trial

Abstract

Summary Background Treatment of chronic drug‐induced liver injury (DILI) or herb‐induced liver injury(HILI) is an important and unresolved challenge. There is no consensus regarding the indications for corticosteroids for chronic DILI/HILI. Aims To investigate the efficacy and safety of corticosteroid plus glycyrrhizin for patients with chronic DILI/HILI. Methods This was a randomised open‐label trial. Eligible patients with causality assessment using the updated RUCAM were randomly assigned (1:1) either to the steroid treatment group (48‐week stepwise dose reduction of methylprednisolone plus glycyrrhizin) or control group (glycyrrhizin alone). Liver biopsies were performed at baseline and at the end of the 48‐week treatment period. The primary outcome was the proportion of patients with sustained biochemical response (SBR). The secondary outcomes were improvement in liver histology, time to biochemical normalisation and safety. Results Of 80 participants, 70 (87.5%) completed the trial. The patients were predominantly female (77.5%), aged >40 years (77.5%) and had a hepatocellular injury pattern of DILI (71.2%). Compared to the control group, the treatment group showed a higher proportion of SBR (94.3% vs. 71.4%, p = 0.023), shorter biochemical normalisation time and histological improvements in both histological activity and fibrosis. The DILI and HILI subgroups, as well as the autoimmune hepatitis (AIH)‐like DILI and non‐AIH‐like subgroups, showed comparable responses. No severe adverse events were observed during the trial. Conclusion This study provides the first clinical evidence that corticosteroid plus glycyrrhizin therapy for chronic DILI with or without AIH‐like features can achieve both biochemical response and histological improvements with good safety. (http://clinicaltrials.gov, NCT 02651350).

Editorial: chronic DILI and HILI—corticosteroid plus glycyrrhizin as standard therapy? Authors' reply

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We would like to thank Rolf Teschke and Axel Eickhoff for their interest in our work investigating the efficacy and safety of corticosteroid (CS) plus glycyrrhizin (GC) therapy for chronic drug-or herb-induced liver injury (DILI/HILI). 1,2 Cessation of the suspected agent(s) is widely recommended and convincingly proved to reverse 80% DILI in the acute phase, 3,4 but this strategy seemed not contributable for patients in our study. It is worth to note that all the participants in two groups of this study have experienced drug cessation at least 6 months prior to therapy, suggesting they had already been patients with chronic DILI and drug cessation alone is not sufficient for DILI intervention.

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“…The authors' declarations of personal and financial interests are unchanged from those in the original article. 2 Jia-Bo Wang…”

“…We would like to thank Rolf Teschke and Axel Eickhoff for their interest in our work investigating the efficacy and safety of corticosteroid (CS) plus glycyrrhizin (GC) therapy for chronic drug‐or herb‐induced liver injury (DILI/HILI) 1,2 …”

Editorial: chronic DILI and HILI – corticosteroid plus glycyrrhizin as standard therapy?

“…The recently published study by Jia‐bo Wang et al 10 found a better efficacy of CSs combined with GC as compared with GC alone in patients with chronic DILI and HILI. No death or liver transplantation was reported.…”

“…Limitations of the study included the retrospective design, the randomised open‐label trial approach instead of an RCT, the use of GC as a not approved regulatory herbal medicine in Western countries, and the low case number 10 . The conclusion is reached that expansion of the study is needed before CSs + GC can be promoted as standard therapy.…”